Endocytosis of a chimera between human pro‐urokinase and the plant toxin saporin: an unusual internalization mechanism
Endocytosis of a chimera between human pro‐urokinase and the plant toxin saporin: an unusual internalization mechanism
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人尿激酶原和植物毒素肥皂草素之间嵌合体的内吞作用：一种不寻常的内化机制
DOI：
10.1096/fasebj.14.10.1335
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
M. Fabbrini
中科院分区：
文献类型：
--
作者：
R. Ippoliti;E. Lendaro;P. A. Benedetti;M. Torrisi;F. Belleudi;D. Carpani;M. Soria;M. Fabbrini
为了研究这种潜在的抗肿瘤结合物在转人尿激酶受体基因的小鼠模型细胞系LB6 Clone19(Cl19)中的吞噬作用，制备了人尿激酶原与植物核糖体失活蛋白SapTRITC之间的嵌合毒素的荧光衍生物。尿激酶抑制物复合体的生理内化是由纤溶酶原抑制物(PAI)与低密度脂蛋白相关受体蛋白(LRP)家族的受体相互作用而触发的，涉及包括uPAR、LRP和PAI在内的大的四级结构。然而，与这一机制相反，我们观察到了一个两步过程：首先，尿激酶受体(UPAR)充当质膜上的锚定因子；随后，LRP充当内吞触发器。一旦嵌合体通过与uPAR的相互作用结合到质膜上，我们认为可能发生了一种交换，通过皂苷部分将毒素转移到LRP，并开始内化。因此，描述了一种不寻常的内吞过程，其中毒素通过不同于用于结合质膜的受体进入细胞。-Ippoliti，R.，Lendaro，E.，Benederti，P.A.，Torrisi，M.R.，Bellleudi，F.，Carpani，D.，Soria，M.R.，Fabbrini，M.S.人尿激酶原和植物毒素Saporin之间的嵌合体的内吞作用：一种不寻常的内化机制。FASE B J.14,1335-1344(2000)
A fluorescent derivative of a chimeric toxin between human pro‐urokinase and the plant ribo‐some‐inactivating protein saporin (p‐uPA‐SapTRITC), has been prepared in order to study the endocytosis of this potentially antimetastatic conjugate in the murine model cell line LB6 clone19 (Cl19) transfected with the human urokinase receptor gene. The physiological internalization of urokinase‐inhibitor complexes is triggered by the interaction of plasminogen inhibitors (PAIs) with receptors belonging to the low density lipoprotein‐related receptor protein (LRP) family, and involves a macro‐quaternary structure including uPAR, LRP, and PAIs. However, in contrast to this mechanism, we observed a two‐step process: first, the urokinase receptor (uPAR) acts as the anchoring factor on the plasma membrane; subsequently, LRP acts as the endocytic trigger. Once the chimera is bound to the plasma membrane by interaction with uPAR, we suggest that a possible exchange may occur to transfer the toxin to LRP via the saporin moiety and begin the internalization. So an unusual endocytic process is described, where the toxin enters the cell via a receptor different from that used to bind the plasma membrane.—Ippoliti, R., Lendaro, E., Benedetti, P. A., Torrisi, M. R., Belleudi, F., Carpani, D., Soria, M. R., Fabbrini, M. S. Endocytosis of a chimera between human pro‐urokinase and the plant toxin saporin: an unusual internalization mechanism. FASEB J. 14, 1335–1344 (2000)
体外损伤后，迁移的血管平滑肌细胞使细胞表面尿激酶受体极化。
影响因子：
3.7
作者：
Okada,SS;Tomaszewski,JE;Barnathan,ES
通讯作者：
Barnathan,ES